The ever increasing emergence of many relevant pathogenic strains of bacteria resistant to commonly used antibiotics is a rapidly growing concern in public health. Patients with weakened immunity because of chemotherapy, AIDS or organ transplantation or patients undergoing acute care in hospitals are significantly at risk for acquiring opportunistic bacterial infections. Seven leading groups of pathogens account for the increased risk for such infections, including Gram-positive bacteria: Staphylococcus aureus, Enterococcus faecium, streptococci, and coagulase-negative staphylococci. Resistance against commonly used classical antibiotics has emerged in all of these pathogens. Given the increasing rate at which infectious organisms develop resistance to antibiotics currently in use, there is an urgent need to develop novel classes of potent antibiotics against molecular targets, such as lipid II. Lipid II is an ideal target for antibiotics since it is an essential component in bacterial cell wall synthesis. Strategies to find novel antimicrobial (antibacterial) compounds using bacterial genomics approaches have as yet proven largely unsuccessful.